Abstract. The incidence and mortality rates of gastric cancer are one of the highest of all types of cancers. Emerging evidence has demonstrated that altered expression of micro (mi)RNAs may be implicated in the tumorigenesis of numerous types of cancer. Therefore, miRNAs may have potential as important tools in cancer diagnostics and therapeutics. miRNAs regulate the expression of genes involved in mediating cell proliferation and developmental timing, among numerous other processes. Altered expression levels of miRNAs may result in the ability of cells to proliferate aberrantly and migrate. The present study used reverse transcription-quantitative polymerase chain reaction assays to analyze miRNA-577 expression in gastric cancer tissues and cell lines, MTT and cell cycle analysis to examine cell proliferation in vitro, and luciferase assays and western blot to investigate miRNA-577's downstream targets. The results demonstrated that miRNA-577 was significantly downregulated in gastric cancer patient samples and cell lines. In addition, miRNA-577 affected an important regulator of E2F transcription factor 3 expression and that altered miRNA-577 expression resulted in the aberrant proliferation of gastric cancer cells.
Colorectal cancer (CRC) is the third most commonly diagnosed malignancy that is associated with high levels of mortality. CRCs are often associated with an aberrant wingless-type mouse mammary tumor virus integration site family (Wnt) signaling pathway known to be responsible for tumorigenesis and cancer progression. Other factors that contribute to CRC pathology include hypoxia, extracellular matrix and cellular microenvironment. In the present study, modulation of Wnt, a common molecular progenitor for CRC-associated pathology was evaluated. CRC tissues and specific cell lines were found to exhibit increased expression levels of prolyl 4-hydroxylase subunit α1 (P4HA1). P4HA1 expression was found to stabilize hypoxia inducible factor-1α (HIF1α). The silencing of P4HA1 resulted in decreased cell proliferation, cell cycle arrest in the G 1 phase, decreased tumorsphere formation, decreased tumorsphere volume, increased susceptibility to 5-fluorouracil and increased caspase-3 activity. However, P4HA1 silencing resulted in the activation and thus proteasomal degradation of β-catenin, indicative of the abrogation of Wnt signaling pathway. Wnt is a critical signaling pathway and is activated in most CRCs. HIF1α is a poor prognostic marker in CRC. The present study provided preliminary evidence that HIF1α and the Wnt signaling pathway in CRC are modulated through P4HA1. P4HA1 may serve not just as a biomarker for CRC prognosis but may also be targeted for potential therapeutic intervention.
The increasing burden of diabetes in low and middle-income countries is attributable to both genetic and epigenetic factors. environmental-and lifestyle-associated changes are also considered to be important contributors to this disease. The resultant co-morbidities arising from micro-and macrovascular changes in diabetes are difficult to manage and are an economic burden. However, very little is known about the molecular mechanisms that drive this phenotype. The present study aimed to investigate the role of sirtuin 1 (SirT1)-and transcription box-3 (TBX-3)-mediated regulation of endothelial dysfunction, given the significance of SIRT1 in glucose metabolism and the role of TBX-3 in the maintenance of cellular proliferation, senescence and apoptosis. Following the recruitment of adult patients with and without diabetes, both SIRT1 and TBX-3 expression was confirmed to be present in the sera of the patients with diabetes and the patients without diabetes; however, both SirT1 and TBX-3 expression levels were higher in the sera of the patients with diabetes. Human umbilical vein endothelial cells (HuVecs) were further used for in vitro studies. using TBX-3 and SirT1 knockdown models, the cellular responses to proliferation, migration, invasion and tube formation were investigated using an MTS, cell cycle analysis, wound healing, Transwell and tube formation assay, respectively. Western blotting was also used to determine the downstream signaling pathways involved. The genetic knockdown of TBX-3 in hyperglycemic conditions significantly decreased the cellular proliferation, migration, invasion and angiogenesis of HuVecs. it was subsequently identified that TBX-3 mediated its effects through the activation of aKT and vascular endothelial growth factor (VeGF) signaling. However, the genetic knockdown of SirT1 in the presence of TBX-3 overexpression and glucose failed to activate the aKT and VeGF signaling pathways. in conclusion, the results of the present study suggested that SirT1 may positively regulate TBX-3 in endothelial cells, therefore, SirT1 and/or TBX-3 may serve as potential novel biomarkers for disease progression.
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